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A global ocean circulation model is coupled to a Lagrangian particle tracking model to simulate 30 years of input, transport and accumulation of floating debris in the world ocean. Using both terrestrial and maritime inputs, the modelling results clearly show the formation of five accumulation zones in the subtropical latitudes of the major ocean basins. The relative size and concentration of each clearly illustrate the dominance of the accumulation zones in the northern hemisphere, while smaller seas surrounded by densely populated areas are also shown to have a high concentration of floating debris. We also determine the relative contribution of different source regions to the total amount of material in a particular accumulation zone. This study provides a framework for describing the transport, distribution and accumulation of floating marine debris and can be continuously updated and adapted to assess scenarios reflecting changes in the production and disposal of plastic worldwide., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The main effects of antagonistic rhizobacteria on plant pathogenic fungi are antibiosis, fungistasis or an indirect constraint through the induction of a plant defence response. To explore different biocontrol mechanisms, an in vitro confrontation assay was conducted with the rhizobacterium Pseudomonas fluorescens Pf29Arp as a biocontrol agent of the fungus Gaeumannomyces graminis var. tritici (Ggt) on wheat roots. In parallel with the assessment of disease extension, together with the bacterial and fungal root colonization rates, the transcript levels of candidate fungal pathogenicity and plant-induced genes were monitored during the 10-day infection process. The bacterial inoculation of wheat roots with the Pf29Arp strain reduced the development of Ggt-induced disease expressed as attack frequency and necrosis length. The growth rates of Ggt and Pf29Arp, monitored through quantitative polymerase chain reaction of DNA amounts with a part of the Ggt 18S rDNA gene and a specific Pf29Arp strain detection probe, respectively, increased throughout the interactions. Bacterial antagonism and colonization had no significant effect on root colonization by Ggt. The expression of fungal and plant genes was quantified in planta by quantitative reverse transcription-polymerase chain reaction during the interactions thanks to the design of specific primers and an innovative universal reference system. During the early stages of the tripartite interaction, several of the fungal genes assayed were down-regulated by Pf29Arp, including two laccases, a β-1,3-exoglucanase and a mitogen-activated protein kinase. The plant host glutathione-S-transferase gene was induced by Ggt alone and up-regulated by Pf29Arp bacteria in interaction with the pathogen. We conclude that Pf29Arp antagonism acts through the alteration of fungal pathogenesis and probably through the activation of host defences., (© 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.)

Purpose: To test the efficiency of locally administrated tresperimus in experimental autoimmune uveoretinitis (EAU)., Methods: EAU was induced in Lewis rats by S-antigen (S-Ag) immunization. Three intravitreal injections of tresperimus (prevention or prevention/treatment protocols) were performed at different time points after immunization. The pharmacokinetics of tresperimus was evaluated in the ocular tissues and plasma. The in vitro effect of tresperimus was evaluated on macrophages. EAU was graded clinically and histologically. Blood ocular barrier permeability was evaluated by protein concentration in ocular fluids. Immune response to S-Ag was examined by delayed type hypersensitivity, the expression of inflammatory cytokines in lymph nodes, ocular fluids and serum by multiplex ELISA, and in ocular cells by RT-PCR., Results: In vitro, tresperimus significantly reduced the production of inflammatory cytokines by lipopolysaccharide-stimulated macrophages. In vivo, in the treatment protocol, efficient tresperimus levels were measured in the eye but not in the plasma up to 8 days after the last injection. Tresperimus efficiently reduced inflammation, retinal damage, and blood ocular barrier permeability breakdown. It inhibited nitric oxide synthase-2 and nuclear factor κBp65 expression in ocular macrophages. IL-2 and IL-17 were decreased in ocular media, while IL-18 was increased. By contrast, IL-2 and IL-17 levels were not modified in inguinal lymph nodes draining the immunization site. Moreover, cytokine levels in serum and delayed type hypersensitivity to S-Ag were not different in control and treated rats. In the prevention/treatment protocol, ocular immunosuppressive effects were also observed., Conclusions: Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation.

In order to investigate potential links existing between Gaeumannomyces graminis var. tritici (Ggt) population structure and disease development during polyetic take-all epidemics in sequences of Ggt host cereals, seven epidemics in fields with different cropping histories were monitored during the seasons 2001/2002 (two fields), 2002/2003 (two fields) and 2003/2004 (three fields). Take-all incidence and severity were measured at stem elongation and Ggt populations were characterized. The 73 isolates collected in the two fields in 2001/2002 were distributed into two multilocus genotypes, G1 and G2 according to amplified fragment length polymorphism analysis. A monolocus molecular marker amplified by F-12 random amplification polymorphism DNA primer sizing between 1.9 and 2.0 kb that gave strictly the same distinction between the two multilocus genotypes was further applied to measure G1/G2 frequencies among Ggt populations in all fields (266 isolates). The ratios of G1 to G2 differed between fields with different cropping histories. A linear relationship between G2 frequency among Ggt populations and disease severity at stem elongation was measured during the three cropping seasons. When take-all decline was observed, G2 frequencies were low in first wheat crops, highest in short-term sequences and intermediate in longer sequences of consecutive crops of Ggt host cereals. This pattern could be the result of population selection by environmental conditions, in particular by microbial antagonism during the parasitic phase of the fungus. In order to better understand take-all epidemic dynamics, the distinction between these two genotypes could be a basis to develop models that link approaches of quantitative epidemiology and advances in population genetics of Ggt.

The neutron energy distribution of the IRSN standard 241Am-Be(alpha,n) source was measured using a proton recoil liquid scintillator, BC501A, >1.65 MeV. The experimental data were compared with the ISO recommended neutron energy distribution for an Am-Be source and some significant discrepancies were observed. Monte Carlo simulations were then performed to investigate on the neutron source term in order to consider the different parameters between the IRSN Am-Be source and the one used to establish the neutron emission spectrum recommended by the ISO standard. The variation of the parameters of the source did not explain the remaining discrepancies. A good agreement with the experimental results was observed when the theoretical neutron energy distribution from Geiger and Van der Zwan was introduced in the study as new source term. These investigations showed that the ISO recommended Am-Be distribution might not be well suited to represent the neutron energy distribution of all Am-Be sources, and that the manufacturing of the sources might play a major role in the neutron fluence energy distribution.

A method was developed to assess the genetic structure of Gaeumannomyces graminis var. tritici (Ggt) populations and test the hypothesis of an association between disease level in the field with changes in pathogen populations. A long-term wheat monoculture experiment, established since 1994, generated different take-all epidemics with varying the number of wheat crop successions in the 1999-2000 cropping season. Genetic polymorphism in Ggt populations was investigated over natural, local epidemics. Four populations of 30 isolates were isolated from necrotic wheat roots in a first, third, fourth, and sixth wheat crop in the same year. Each Ggt isolate was characterized with RAPD (Random Amplification Polymorphism DNA) markers and AFLP (Amplified Fragment Length Polymorphism) fingerprinting. Seventeen multilocus genotypes based on the combination of RAPD and AFLP markers were identified among all these populations. The 120 isolates were divided into two main groups, G1 and G2, according to bootstrap values higher than 86%, except for an unique isolate from the third wheat crop. Within each group, populations ranged between 93 and 100% similarity. Both groups included isolates collected from the first, third, fourth or sixth wheat crop. However, G1 group profiles dominated amongst isolates sampled in the first and the sixth wheat crops, whereas G2 group profiles largely dominated amongst isolates collected from the third and fourth wheat crops. Aggressiveness of group G2 (38%) was significantly greater than that of G1 (29.5%). These results suggest that changes in Ggt population structure occur during continuous wheat cropping. The distinction of two Ggt groups provides a simple basis for further spatio-temporal analysis of Ggt population during polyetic take-all decline.

A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine "D" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene alpha to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60e which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.

ABSTRACT To test the hypothesis that host-related differences in the genotypic composition of populations of the late blight pathogen Phytophthora infestans can be explained by differential pathogenicity, the aggressiveness of isolates of the pathogen collected in France from potato and tomato was measured on detached leaflets of potato (cv. Bintje) and tomato (cv. Marmande). A preliminary trial with four isolates (two each from potato and tomato) showed that lesion appearance and development were similar for each isolate in detached leaflets and in whole plant tests in growth cabinets. Isolates collected from tomato were more pathogenic to tomato than isolates collected from potato. This was particularly the case for isolates belonging to the A2 mating type. Isolates originating from potato had a higher infection efficiency and a higher sporulation capacity on this host, but they induced lesions that generally spread more slowly than those caused by isolates from tomato. Extensive variation for components of aggressiveness on potato, and to a lesser extent on tomato, was observed in collections of isolates from each of the two hosts. Competition experiments between one potato isolate and one tomato isolate in field plots of the susceptible potato cv. Bintje clearly demonstrated the higher competitive fitness of the potato isolate on its host of origin. Therefore, differential pathogenicity to potato and tomato certainly contributes to the differentiation between P. infestans populations present on potato and tomato in France; however, additional factors, possibly related to survival ability or random genetic drift, are probably also involved and may explain the persistence of weakly pathogenic isolates in these populations.

A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

Twenty new 2-(cyanoalkyl)tetrazoles (15 and 16) and twenty new 2-(hydroxyalkyl)tetrazoles (17 and 18) were synthesized and investigated in vitro for their abilities to inhibit selectively rat brain monoamine oxidase (MAO) B over MAO A. Most of them were MAO B inhibitors and those bearing a substituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 microM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37,000 for 16a. The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests. The 5-[4-(phenylmethoxy)phenyl]-2-(2-cyanoethyl)tetrazole (16a) its derivative 16h and the 5-[4-(phenylmethoxy)phenyl]-2-(2-hydroxyethyl)tetrazole (18a) and its derivative 18h were found to be potent, in vitro selective, and competitive MAO B inhibitors. Tetrazole 16a can be considered one of the most active and selective competitive MAO B inhibitors known up to now. This compound was selected for ex vivo experiments and was shown to be a strong and reversible MAO B inhibitor with a short duration of action after oral administration at 5 mg/kg. The structure-activity approach gives rise to the great importance of lipophilicity over electronic effects of the compounds in these series.

The authors present the results of 69 cases operated between 1983 and 1989. The indications were dominated by two aetiologies: degenerative lesions of the inferior radio-ulnar joint in rheumatoid arthritis: 58% of cases, and traumatic sequelae, predominantly secondary to fractures of the distal radius: 34% of cases. The authors stress the effects of distant lesions: skeletal lesions of the two bones of the forearm or the superior radio-ulnar joint. A third group of rarer indications consisted of painful dislocations of the inferior radio-ulnar joint in Madelung's disease (indication only applied to adults). There were two types of complications: complications due to excessively long or intra-articular screws, which were treated by removal of the screws and, more severe, ossifications of the zone of diaphyseal resection (5 cases) which interfered with the functional result in terms of mobility. Three cases required extensive diaphyseal resection. The results are analysed for each aetiological group in terms of pain, mobility prehensile strength after more than one year of follow-up. Good results were obtained in 80% of cases of post-traumatic lesions (16 cases). The insufficient results were related to associated lesions of the elbow or the 2 bones of the forearm. A good result was obtained in 3 out of 4 cases of Madelung's disease and one case, operated elsewhere and revised by pseudoarthrodesis, obtained a moderate result. Lastly, in rheumatoid arthritis, the results in terms of pain, mobility and prehensile strength were good, apart from 2 failures due to progression of rheumatoid disease (cases unsuitable for this treatment). Radiographic analysis according to Youm and Mac Murtry's criteria showed minimal regression in the carpoulnar translation index (pre-op: 0.28; post-op: 0.22). Overall, the Sauvé-Kapandji operation provided good quality clinical results when the indications and technique were rigorously applied.